Plasma sTWEAK levels in chronic kidney disease stages
Abstract
Objective: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a cytokine of the TNF superfamily that has a role in injury of different organs including kidney. We hypothesized that in patients with chronic kidney disease (CKD), sTWEAK levels may be related to endothelial dysfunction that usually accompanies the decline of estimated glomerular filtration rate (eGFR). Methods: In 199 patients with different stages of CKD we examined the relationship between sTWEAK plasma levels and CKD stages and the relationship between high sensitivity C reactive protein (hs-CRP), homeostatic model assessment of insulin resistance (HOMA-IR) and sTWEAK concentrations. Results: A gradual decrease in sTWEAK was observed as eGFR decreased. sTWEAK plasma levels were diminished in all stages of CKD and strongly correlated with eGFR. A negative correlation was found between sTWEAK and hs-CRP (p=<0.001) and while a positive correlation was found between sTWEAK and eGFR (p=<0.001). No significant correlation was found between sTWEAK and HOMA-IR. In multivariate regression eGFR, diabetes mellitus and hs-CRP parameters were found to be significant independent variables in decreasing plasma sTWEAK levels. Conclusion: Diminishing of eGFR is accompanied by gradual decreases in sTWEAK plasma levels. Since sTWEAK is strongly and independently correlated with CRP, our study reveals new connections between sTWEAK and endothelial dysfunction in patients with CKD.
References
2) Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(5 Suppl. 3):S112-9. doi: 10.1053/ajkd.1998.v32.pm9820470.
3) Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15(8):1983-92. doi: 10.1097/01.ASN.0000132474.50966.DA.
4) Tonelli M, Pfeffer MA. Kidney disease and cardiovascular risk. Annu Rev Med. 2007;58:123-39. doi: 10.1146/annurev.med.58.071105.111123.
5) Yilmaz MI, Carrero JJ, Ortiz A, Martín-Ventura JL, Sonmez A, Saglam M, et al. Soluble TWEAK plasma levels as a novel biomarker of endothelial function in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(11):1716-23. doi: 10.2215/CJN.02760409.
6) Fernández-Laso V, Sastre C, Valdivielso JM, Betriu A, Fernández E, Egido J, et al. Soluble TWEAK and major adverse cardiovascular events in patients with CKD. Clin J Am Soc Nephrol. 2016;11(3):413-22. doi: 10.2215/CJN.07900715.
7) Ortiz A, Sanz AB, Muñoz García B, Moreno JA, Sánchez Niño MD, Martín-Ventura JL, et al. Considering TWEAK as a target for therapy in renal and vascular injury. Cytokine Growth Factor Rev. 2009;20(3):251-8. doi: 10.1016/j.cytogfr.2009.05.002.
8) Muntner P, Hamm LL, Kusek JW, Chen J, Whelton PK, He J. The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease. Ann Intern Med. 2004;140(1):9-17. doi: 10.7326/0003-4819-140-1-200401060-00006.
9) Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA. 2004;291(4):451-9. doi: 10.1001/jama.291.4.451.
10) National Kidney Foundation. Chronic Kidney Disease, Classification [Internet]. Disponible en: https://www.kidney.org/professionals/guidelines/guidelines_commentaries/chronic-kidney-disease-classification (consulta: 28/01/2021).
11) Kralisch S, Ziegelmeier M, Bachmann A, Seeger J, Lössner U, Blüher M, et al. Serum levels of the atherosclerosis biomarker sTWEAK are decreased in type 2 diabetes and end-stage renal disease. Atherosclerosis. 2008;199(2):440-4. doi: 10.1016/j.atherosclerosis.2007.10.022.
12) Fernández-Laso V, Méndez-Barbero N, Valdivielso JM, Betriu A, Fernández E, Egido J, et al. Soluble TWEAK and atheromatosis progression in patients with chronic kidney disease. Atherosclerosis. 2017;260:130-7. doi: 10.1016/j.atherosclerosis.2017.03.043.
13) Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology, and therapeutic targeting. Nat Rev Drug Discov. 2008;7(5):411-25. doi: 10.1038/nrd2488.
14) Carrero JJ, Ortiz A, Qureshi AR, Martín-Ventura JL, Bárány P, Heimbürger O, et al. Additive effects of soluble TWEAK and inflammation on mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2009;4(1):110-8. doi: 10.2215/CJN.02790608.
15) Blanco-Colio LM, Martín-Ventura JL, Muñóz-García B, Orbe J, Páramo JA, Michel JB, et al. Identification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(4):916-22. doi: 10.1161/01.ATV.0000258972.10109.ff.
16) Shi X, Qiu B, Shen H, Feng S, Fu J. Inverse relationship between plasma tumor necrosis factor-like weak inducer of apoptosis and carotid intima-media thickness among patients undergoing hemodialysis and peritoneal dialysis. Cardiorenal Med. 2020;10(3):137-44. doi: 10.1159/000503811.
17) Hénaut L, Sanz AB, Martin-Sanchez D, Carrasco S, Villa-Bellosta R, Aldamiz-Echevarria G, et al. TWEAK favors phosphate-induced calcification of vascular smooth muscle cells through canonical and non-canonical activation of NFκB. Cell Death Dis. 2016;7(7):e2305. doi: 10.1038/cddis.2016.220.
Copyright (c) 2022 Revista de Nefrología, Diálisis y Trasplante
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
